Mitofusin 2 inhibits mitochondrial antiviral signaling

Kai Yasukawa, Hiroyuki Oshiumi, Makoto Takeda, Naotada Ishihara, Yusuke Yanagi, Tsukasa Seya, Shun Ichiro Kawabata, Takumi Koshiba

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

The innate immune response to viral infection involves the activation of multiple signaling steps that culminate in the production of type I interferons (IFNs). Mitochondrial antiviral signaling (MAVS), a mitochondrial outer membrane adaptor protein, plays an important role in this process. Here, we report that mitofusin 2 (Mfn2), a mediator of mitochondrial fusion, interacts with MAVS to modulate antiviral immunity. Overexpression of Mfn2 resulted in the inhibition of retinoic acid-inducible gene I (RIG-I) and melanoma differentiation- associated gene 5 (MDA-5), two cytosolic sensors of viral RNA, as well as of MAVS-mediated activation of the transcription factors interferon regulatory factor 3 (IRF-3) and nuclear factor κB (NF-κB). In contrast, loss of endogenous Mfn2 enhanced virus-induced production of IFN-β and thereby decreased viral replication. Structure-function analysis revealed that Mfn2 interacted with the carboxyl-terminal region of MAVS through a heptad repeat region, providing a structural perspective on the regulation of the mitochondrial antiviral response. Our results suggest that Mfn2 acts as an inhibitor of antiviral signaling, a function that may be distinct from its role in mitochondrial dynamics.

Original languageEnglish
Pages (from-to)ra47
JournalScience Signaling
Volume2
Issue number84
DOIs
Publication statusPublished - Aug 18 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Mitofusin 2 inhibits mitochondrial antiviral signaling'. Together they form a unique fingerprint.

  • Cite this

    Yasukawa, K., Oshiumi, H., Takeda, M., Ishihara, N., Yanagi, Y., Seya, T., Kawabata, S. I., & Koshiba, T. (2009). Mitofusin 2 inhibits mitochondrial antiviral signaling. Science Signaling, 2(84), ra47. https://doi.org/10.1126/scisignal.2000287